Abstract: Herbicide injury is an unavoidable issue in the general use of herbicides. The most direct and effective approach to solve the problem of herbicide injury is to apply herbicide safeners. Herbicide safeners are a variety of agricultural chemicals that selectively protect crops from herbicide damage, without affecting herbicidal efficacy to target weeds. Commercial safeners were found to cause some risks to the agricultural ecological environment during long-term application. Natural safeners, discovered from endogenous compounds in animals, plants, and microorganisms, are novel in structure and relatively friendly to the ecological environment. Using natural safeners provides an effective way to solve the potential risks of commercialized safeners to the environment. This paper reviewed the research progress of natural safeners in the aspects of discovery methods, structures, and the effects of alleviating herbicide injuries to crop plants. The mechanism of existing natural safeners protecting crops against herbicide injury was summarized. The limitations used under field conditions and future research directions of natural safeners were concluded and prospected, respectively. These could provide guidance for the practical application of natural safeners in the prevention of herbicide injury and the development of corresponding products.